Epidemiologic analysis of acute, reversible respiratory health effects is uncommonly performed, yet these are important health outcomes because acute responses by the respiratory defense system appear to represent one end of the continuum toward progressive, chronic and potentially disabling physiologic changes. Repeatable epidemiologic studies of dose-response relationships necessitate accurate measures of "dose". However, in occupational and environmental settings, exposure to a toxin is seldom found at identical concentrations and/or particle sizes among persons with the same activity patterns. In addition, air concentration does not account for factors such as clearance or metabolism which may alter the biologically effective tissue dose. Since these factors cause the target tissue dose of the toxin to vary greatly despite exposure to similar air concentrations, a central goal of this study is to modify and expand an existing pharmacokinetic model for nasal dose as well as to develop a new model to estimate tracheobronchial dose of an active agent for each subject in a study of acute respiratory health effects. The results of these toxicokinetic models will be individual measures of tissue dose to be used in a 2-stage epidemiologic analysis which places special emphasis on the definition of individual dose-response curves for exposure to an irritant dust, sodium borate, and the reversible effects of peak expiratory flow and irritant symptoms. A primary advantage of the two stage epidemiologic approach is that it permits particular attention to be focused on the factors which determine the sensitivity (threshold) and reactivity (slope) for an individual. The use of tissue dose estimates will also be compared to simple exposure measurements in the epidemiologic analysis to evaluate the efficacy of using dosimetric methods in epidemiologic studies. The data available for this proposal derive from a recent study of acute irritation in a cohort of workers exposed to sodium borate dusts. This data set includes repeated daily measurements of changes in peak expiratory flow and symptoms of irritation with matched continuous monitoring of personal airborne particle exposures in the production of sodium borate products.